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Biomedical subjects

B M Brenner

Publications and source records attributed to B M Brenner.

At least 271 records · Page 15Linked to original sources
PubMed1980

Effect of verapamil on the hydroosmotic response to antidiuretic hormone in toad urinary bladder.

To investigate the role of the calcium ion in the hydroosmotic response to antidiuretic hormone (ADH), the effects of verapamil, an inhibitor of calcium ion entry into cells, on stimulated water flow was examined in vitro in the toad urinary bladder. Verapamil, 50 micro M, decreased ADH-stimulated osmotic water flow from 23.4 +/- 4.1 to 9.9 +/- 3.3 mg . min-1 . hemibladder-1 (mean +/- SE, n = 12, P < 0.001). That this inhibitory effect was due to a verapamil-induced alteration in cellular calcium metabolism is suggested by the findings that 45Ca2+ uptake by isolated toad bladder epithelial cells was reduced nearly 50% in the presence of verapamil and that reversibility of verapamil's inhibitory action was calcium dependent. Additionally, verapamil reduced theophylline- (20 mM) stimulated water flow from 22.8 +/- 2.7 to 9.5 +/- 2.9 mg . min-1 . hemibladder-1 (n = 7, P < 0.001) but enhanced cAMP- (10 mM) induced water flow from 12.8 +/- 2.5 to 21.6 +/- 1.1 ng . min-1 . hemibladder-1 (n = 7, P < 0.001). The latter effect was due, at least in part, to a direct inhibitory effect by verapamil on phosphodiesterase activity of toad bladder homogenates. These results, therefore, suggest that the calcium ion is an important coupling factor at the level of the adenylate cyclase enzyme complex for the stimulus-reabsorption coupling between ADH and the transporting epithelia of the toad urinary bladder.

Animals↗
PubMed1980

Effects of parathyroid hormone on glomerular function.

Acute thyroparathyroidectomy (TPTX) in rats results in a marked increase in the glomerular capillary ultrafiltration coefficient, Kf. Infusion of a submaximal dose of bovine PTH (1 U/kg/min) returns Kf to non-TPTX levels. Infusion of 10 U/kg/min of bovine PTH further reduces Kf and leads to a net reduction in single nephron GFR. These findings suggest that PTH may play an important role in modulating Kf and, consequently, GFR.

Animals↗
PubMed1980

Importance of efferent arteriolar vascular tone in regulation of proximal tubule fluid reabsorption and glomerulotubular balance in the rat.

Micropuncture study was performed in 21 mildly volume-expanded Munich-Wistar rats before and during partial aortic constriction to examine the effects of endogenous prostaglandins (PG) and angiotensin II (AII) on single nephron glomerular filtration rate (SNGFR) and absolute proximal reabsorption rate (APR). Animals received either vehicle (group 1), indomethacin (group 2), or indomethacin plus saralasin (group 3). Before aortic constriction, these inhibitors were without effect on values of SNGFR and APR. In group 1 rats, reduction in mean renal arterial perfusion pressure (RAP) to approximately 65 mm Hg resulted in marked and proportional declines in SNGFR and APR. With equivalent reduction in RAP in group 2 rats, however, SNGFR fell to a lesser extent and APR tended to increase slightly above preconstriction values. Indomethacin administration was therefore associated with disruption of glomerulotubular balance. In view of the roughly equivalent declines in afferent arteriolar resistance measured in groups 1 and 2, the magnitude of increase in efferent arteriolar resistance (R(E)) appeared to be of major importance in determining the observed presence or absence of glomerulotubular balance. Thus, the lesser fall in SNGFR in group 2 than in group 1 was a result of the higher value for glomerular capillary hydraulic pressure in group 2, a consequence of the higher value of R(E). The higher average value for APR during reduced RAP in group 2 than in group 1 is also attributable to this pronounced rise in R(E), the effect of which was to augment the net reabsorptive pressure both by favoring higher postglomerular oncotic pressure and lower downstream (peritubular capillary) hydraulic pressure. Since intrarenal release of AII is enhanced when RAP declines, and because AII is known to raise R(E) selectively, it is likely that endogenous AII brought about the marked increase in R(E) in group 2, which was readily demonstrable only in indomethacin-treated rats, presumably because endogenous PG synthesis was suppressed. In keeping with this conclusion, when the action of endogenous AII was inhibited by saralasin in group 3 rats, reduction in RAP failed to induce a rise in R(E), so that net filtration and reabsorption pressures again declined proportionally, as did SNGFR and APR. The present evidence therefore suggests that glomerulotubular balance is influenced to an important extent by the prevailing vasomotor tone of the efferent arteriole.

Animals↗
PubMed1980

Mechanism of reduced glomerular filtration rate in chronic malnutrition.

To determine the physiological basis for the low glomerular filtration rate in chronic malnutrition, micropuncture studies were performed in Munich-Wistar rats chronically pair-fed isocaloric diets of either low (group 1, nine rats) or high protein content (group 2, nine rats). Despite the absence of hypoalbuminemia, average values for single nephron and total kidney glomerular filtration rate were nearly 35% lower in group 1 than in group 2. Mean values for glomerular capillary and Bowman's space hydraulic pressures were essentially identical in the two groups, thereby excluding glomerular transcapillary hydraulic pressure difference as the cause for the low filtration rates in group 1 animals. On the other hand, average glomerular capillary plasma flow rate and glomerular capillary ultrafiltration coefficient were significantly lower (by approximately 25 and approximately 50%, respectively) in group 1 than in group 2. The fall in glomerular capillary plasma flow rate was the consequence of increased afferent and efferent arteriolar resistances. Plasma and erythrocyte volumes were found to be equal in five additional pairs of group 1 and group 2 rats. Thus, the substantial alterations in the ultrafiltration coefficient, glomerular capillary plasma flow rate, and renal arteriolar resistances responsible for the low filtration rate in group 1 animals were not merely a consequence of decreased circulating blood or plasma volumes. Mean values for glomerular cross sectional area were significantly lower in group 1 than in group 2 despite similar values for kidney weight in the two groups. This reduction in glomerular cross sectional area in group 1 rats is presumed to reflect a decrease in effective filtration surface area and therefore likely accounts, at least in part, for the decline in ultrafiltration coefficient observed in this group.Finally, since the daily caloric intake of group 2 animals was restricted because of pair feeding requirements tied to the group 1 rats, we studied a third group of seven rats (group 3) allowed an ad lib. intake of the same high protein diet as given to group 2 rats. Average values for single nephron glomerular filtration rate and its determinants were found to be indistinguishable between groups 2 and 3. These results suggest that low protein intake, rather than calorie deficiency per se, is primarily responsible for the reduction in filtration rate seen in this experimental model of chronic malnutrition.

Animals↗
PubMed1980

Glomerular dynamics in rats with hereditary hydronephrosis.

Micropuncture and metabolic studies were performed using Sprague-Dawley rats with hereditary hydronephrosis secondary to vesicoureteric reflux. Whole kidney and single nephron glomerular filtration rates in hydronephrotic and nonhydronephrotic rats were essentially identical. Filtration rates were maintained near normal in hydronephrotic rats because of an elevation in the mean glomerular transcapillary hydraulic pressure difference which effectively offsets a lower initial glomerular capillary plasma flow rate and a possible decrease in the glomerular capillary ultrafiltration coefficient relative to nonhydronephrotic rats. Additional renal abnormalities, including a urinary concentrating defect, a renal sodium conserving defect, and calcium apatite nephrolithiasis, were also found in hydronephrotic rats.

Animals↗
PubMed1979

Reversal of renal cortical actions of angiotensin II by verapamil and manganese.

Experiments were performed on 19 euvolemic Munich Wistar rats to examine the role of calcium in the action of angiotensin II(AII) on the glomerular microcirculation. Intravenous infusion of a mildly pressor dose of AII(N = 7 rats) led to a significant rise in mean glomerular capillary hydraulic pressure (PGC) and significant decines in glomerular plasma flow rate (QA) and the ultrafiltration coefficient (Kf). Because of these offsetting effects, single nephron GFR (SNGFR) and total kidney GFR failed to change significantly. Both afferent and efferent arteriolar resistances (RA and RE) increased during AII infusion, on average by approximately 40% and 75%, respectively. Despite continued AII infusion, addition of verapamil led to return of values for PGC, QA, Kf, RA, and RE essentially to pre-AII levels. In 7 other rats, verapamil infusion alone failed to exert significant influences on these indices. Likewise, no significant changes in these measures were observed when this same dose of AII was infused into verapamil-pretreated animals. Moreover, intrarenal arterial injection of a nonpressor dose of AII into 6 other rats also resulted in changes in PGC, QA, Kf, and RE similar to those seen during intravenous infusion, and addition of manganese abolished these effects. Since verapamil and manganese are both known to interfere with excitation-contraction coupling of smooth muscle, perhaps by inhibiting transcellular calcium transport, the present results suggest that the calcium ion may be an important cofactor required for the expression of AII action on the glomerular microcirculation, by affecting mesangial and efferent arteriolar smooth muscle contractility.

Angiotensin II↗
PubMed1979

Macromolecule transport across glomerular capillaries: application of pore theory.

Developments in the hydrodynamic theory of solute transport through porous membranes are reviewed, with emphasis on their application to macromolecule movement across capillary walls. A model that treats the capillary wall as a barrier containing uniform cylindrical pores, and permeating solutes as hard spheres, is shown to be successful in describing the size-selectivity of the glomerulus. Influences of various hemodynamic perturbations on solute transport are also accounted for by this approach. Possible extensions and modification of the theory, to account for the influence of molecular charge and other factors on glomerular permeability properties, are discussed.

Biological Transport↗
PubMed1979

Influence of molecular configuration on the passage of macromolecules across the glomerular capillary wall.

The influence of molecular configuration on the filtration of macromolecules across glomerular capillary walls was examined by comparing fractional clearances of two uncharged polysaccharides of distinctly different molecular configuration in the Munich-Wistar rat. The macromolecules employed were dextran, a slightly branched polymer of glucopyranose, and ficoll, a highly cross-linked copolymer of sucrose and epichlorohydrin. Differences in effective shape between these two polymers were determined from measurements of several physical properties of aqueous solutions containing either dextran or ficoll. It was found that dextran is best represented as a prolate ellipsoid with axial ratios of 4, 9, and 16 for molecules with Stokes-Einstein radii of 22, 32, and 40 A, respectively. On the other hand, ficoll is more closely approximated as spherical since the axial ratio was found to be between 1 and 2 for all molecular sizes. Fractional clearances of dextran and ficoll ranging in effective radius from 18 to 44 A were determined in each of seven Munich-Wistar rats. Fractional clearances of dextran were found to be greater than those of ficoll, the difference being significant for molecular radii ranging from 24 to 44 A. In addition, as shown previously for dextran, ficoll was found to be neither secreted nor reabsorbed by the renal tubules. These results, therefore, suggest that in addition to molecular size and charge, molecular configuration is also a determinant of the filtration of macromolecules across the glomerular capillary wall.

Animals↗
PubMed1979

Local intrarenal vasoconstrictor-vasodilator interactions in mild partial ureteral obstruction.

Micropuncture studies were performed in Munich-Wistar rats with surgically created chronic partial unilateral ureteral obstruction (UUO). Mean values for superficial single nephron (SN)GFR, total GFR, and initial glomerular plasma flow rate (QA) in obstructed kidneys were essentially identical to values in nonobstructed kidneys. Nevertheless, glomerular capillary hydraulic pressure (PGC) was significantly higher in obstructed than in nonobstructed kidneys. This increase in PGC served to offset the markedly reduced glomerular capillary ultrafiltration coefficient that was also confined to the kidneys ipsilateral to the ureteral obstruction. During infusion of indomethacin or meclofenamate, SNGFR and QA decreased significantly, in association with elevations in arteriolar resistances in obstructed kidneys, whereas such changes were not observed in nonobstructed kidneys. The results suggest that local intrarenal factors, rather than circulating or systemic factor(s), bring about functional adaptations to partial ureteral obstruction. In particular, an indomethacin- and meclofenamate-sensitive vasodilator (presumably prostaglandin) plays a role in antagonizing the effects of a simultaneously acting vasoconstrictor which, although not identified, displayed the functional properties of angiotensin II.

Animals↗
PubMed1979

Maturational development of glomerular ultrafiltration in the rat.

To ascertain the cause of low glomerular filtration rate in newborn and immature mammals, we measured glomerular pressures and flows directly in immature (30- to 45-day-old) euvolemic Munich-Wistar rats with surface glomeruli. As with total kidney GFR, single nephron (SN)GFR was found to be significantly lower than in adult rats, on average by 40% when corrected for kidney weight. Equality between efferent oncotic pressure and transglomeruler hydraulic pressure difference (deltaP) was usually achieved in immature rats, indicating that the glomerular capillary ultrafiltration coefficient is not a factor limiting SNGFR and GFR in immature rats. Although the average values for deltaP in immature rats were slightly, albeit significantly, lower than in adults, markedly lower values (79 +/- 5 vs. 136 +/- 10 nl/min per g kidney wt) for glomerular plasma flow rate (QA) proved to be the primary factor responsible for the lower SNGFR and GFR values in immature rats. Considerably higher values for afferent and efferent arteriolar resistances contributed to this low QA state in immature rats.

Aging↗
PubMed1979

Mechanism of inhibition of proximal tubule fluid reabsorption after exposure of the rat kidney to the physical effects of expansion of extracellular fluid volume.

The natriuresis and concomitant decline in absolute proximal reabsorption (APR) that occur in rats in response to saline loading are blunted markedly when renal perfusion pressure is reduced immediately before, but not after, the volume load. To ascertain the mechanism responsible for these differences between early clamp (EC) vs. late clamp (LC), intracapillary and interstitial determinants of peritubular capillary uptake of APR were measured in seven LC and seven EC Munich-Wistar rats before and after isotonic saline loading (80% body wt). With volume expansion in LC animals, we observed a marked decline in APR (averaging 11+/-1 nl/min), associated with large increases in urinary sodium excretion rate, which averaged 8+/-2 mueq/min. In EC, the changes in urinary sodium excretion rate (+1+/-0 mueq/min) and APR (-3+/-1 nl/min) with volume expansion were smaller in magnitude. Since peritubular capillary reabsorption coefficient and mean peritubular transcapillary hydraulic pressure difference did not change with saline loading in LC, the marked fall in APR was attributed primarily to a measured large decline in mean peritubular transcapillary oncotic pressure difference (deltapi). Despite an equivalent mean fall in deltapi with volume expansion in EC, near-constancy of APR was found to be associated with a simultaneous and equivalent decline in mean peritubular transcapillary hydraulic pressure difference (a consequence of decreased mean peritubular capillary hydraulic pressure), which effectively offset the fall in deltapi. These results demonstrate the importance of hydraulic pressure patterns of the peritubular capillaries in modulating APR and are consistent with the view that Starling forces across the postglomerular microcirculation play a fundamental role in determining APR.

Absorption↗